Barrett's esophagus (BE) is an acquired condition of the lower esophagus in which the normal squamous tissue is replaced by a metaplastic columnar mucosa. BE itself is not malignant, but it is the primary risk factor for esophageal adenocarcinoma, and a significant number of patients with BE will have adenocarcinoma at the time of first endoscopy. Currently, examination for dysplasia requires numerous random biopsy samples. This work will complete the development and clinically test an optical instrument for detecting and grading Barrett's dysplasia. Light scattering spectroscopy (LSS) has already been shown to differentiate between normal and diseased tissue conditions in BE patients, but the analysis is complex so the data is analyzed after the procedure is over. The instrument developed by this work will be based on white light LSS, but it will use a special probe design and data reduction algorithm, developed by NLI, enabling real-time results. The probe design makes use of the properties of light scattering by cell nuclei and other tissue components to enable the separation and subtraction of interfering effects, and the characterization of the nuclei, based on using spectral, angular, and polarization characteristics of the scattering processes. The tissue characterization follows from the instrument's quantitative determination of the nuclear size and number density for the surface mucosal cells - two properties commonly used by pathologists. Specifically, NLI will (i) produce the probe, (ii) calculate the data base for the real-time algorithm, (iii) produce the instrument with light source, spectrometer, and embedded computer (suitable for interface with a standard clinical video endoscope), (iv) verify the instrument operation in the laboratory using standard scattering materials, (v) verify the background subtraction properties by using normal and diseased resected colon tissue, and (vi) conduct clinical studies on patients with Barrett's Esophagus.